[Non-enzymatic glycation and oxidative stress in chronic illnesses and diabetes mellitus]

New approaches in biochemistry and molecular biology have increased the knowledge on the pathophysiology of chronic diseases as late diabetic complications, Alzheimer's disease, arteriosclerosis and vascular disease by defining the concept of "AGE-formation and oxidative stress." Nonenzymatic glycation, in which reducing sugars are covalently bound to free aminogroups of macromolecules, results in the formation of Advanced Glycation End products (AGEs) which accumulate during aging and at accelerated rate during the course of diabetes. Glycation accompanying oxidation processes support AGE-formation. AGE-formation changes the physicochemical properties of proteins, lipids and nucleic acids. In addition, binding of AGEs to specific surface receptors induces cellular signalling and cell activation. Interaction of AGEs with one of the receptors, RAGE, generates intracellular oxidative stress, which results in activation of the transcription factor NF-kappa B and subsequent gene expression, which might be relevant in late diabetic complications.

Knowledge of the basis molecular mechanisms allows to understand the interplay of different inducers such as redicals, cytokines, AGE-proteins and amyloid-beta-peptids and to define oxidative stress as a "common endpoint" of cell dysfunction. With respect to therapeutic options it is now possible not only to optimize blood glycemic control, but also to design drugs such as AGE-inhibitors and AGE-"cross-link" breakers. In addition patients with chronic disease associated with increased oxidative stress ay benefit from an antioxidant rich (and AGE protein poor?) nutrition.